The subject matter of this invention resides in the field of pyridine chemistry and finds particular utility in providing commercially practicable processes for oxidizing pyridine bases in an electrochemical flow cell.
Substantial research, both past and current, has focused on the oxidation of alkylpyridines to achieve, in addition to possible intermediates, their corresponding pyridinecarboxylic acids. Such acids are quite valuable as chemical intermediates and corrosion inhibitors.
Among the methodologies used, ammoxidation of monoalkylpyridines has been an important route to first producing cyanopyridines which have in turn been hydrolyzed to their carboxylic acid counterparts [P. I. Pollak and M. Windholz, "Heterocyclic Chemistry-Pyridine and its Derivatives," Supplement to Part Three, (R. A. Abramovitch, ed.), p. 273 (1974)]. Although this synthesis requires two discrete steps, each part can proceed in high yield so that the overall reported yields of acids from their hydrocarbon precursors have been good. Additionally molecular oxygen is the oxidizing agent in such cases which affords economical operation. There has also been reported at least some realization as to selectivity of such ammoxidation processes, although yields were generally low and a mixture of products was observed. Frequently, loss of one of the oxidized fragments was noted [N. Kucharczyk, A. Zvakova, Coll. Czech Chem. Commun., 28, 55 (1963)].
Alkylpyridines have also been oxidized by chemical agents such as potassium permanganate (KMnO.sub.4). However, these reagents are expensive and have caused excessive oxidation and thereby ring degradation, particularly in the case of polyalkylpyridines [Black, Depp., Coroson, J. Org. Chem., 14, 14 (1949); Chichibabin, Ber., 37, 1373 (1904); Plattner, Keller, Boller, Helv. Chim. Acta, 37, 1379 (1954); Solomon, J. Chem. Soc., 934 (1946)].
Other methodologies include nitric acid oxidation which is reported as a more economical route, although often requiring elevated temperatures and pressures [Bengtsson, Acta Chem. Scand., 9, 832 (1955)]. These harsh conditions can in turn cause decarboxylation or loss of carbon dioxide (CO.sub.2) from the resulting product. Catalytic air oxidation has also been reported, but does not appear to have general application either [U.S. Pat. No. 2,437,938], even though selectivity has been achieved in certain cases [U.S. Pat. No. 3,979,400; Mathes, Sauermilch and Klein, Ber, 84, 452 (1951); 86, 584 (1953)]. Still other oxidizing agents have been reported, but all have suffered from lack of generality, excessive cost, and toxicity, pollution, or other problems [U.S. Pat. No. 2,449,906; U.S. Pat. No. 2,513,099; U.S. Pat. No. 2,513,251; Henze, Ber., 67, 750 (1934); Woodward, Badgett and Kaufman, Ind. Eng. Chem., 36, 544 (1944)].
Electrolytic oxidations of certain alkylpyridines have been reported to give reasonable yields in at least some cases. This technique has not achieved the prominence of other methods, however, even though (1) the oxidizing agent is relatively inexpensive, (2) reaction conditions are mild compared to other methodologies, (3) the approach has general application, (4) and prior-experienced toxicity and pollution problems are either nonexistent or minimal. As possible reasons for this lack of acceptance by industry, such electrolytic methods are often difficult to work out experimentally, especially with the polyalkylpyridines, and recognition of their general applicability to fields such as pyridine chemistry has been hampered by conflicting and contradictory reports in the literature. Moreover, advances in cell design technology have lagged seriously behind the existing need and there has been an unwillingness or inability on the part of industry to realize the potential significance and advantages of this technology and to effect its use in the field of pyridine chemistry.
For example, although electro-oxidations have been reported for producing the three isomeric monocarboxylic acids from their monoalkylpyridine precursors, such reports have achieved only moderate yields of less than 45% in all cases except nicotinic acid in which a 70% yield was reported. Processes have also been reported for some of the six isomeric pyridinedicarboxylic acids (notably, quinolinic acid from quinoline in addition to lutidinic acid from 2,4-lutidine and isocinchomeronic acid from 2-methyl-5-ethylpyridine), but with similar failings. Moreover, no processes have been reported to applicant's knowledge for the electrochemical production of 2,6-diacid (dipicolinic), 3,5-diacid (dinicotinic), 2,3-diacid (quinolinic) from 2,3-lutidine, or 3,4-diacid (cinchomeronic).
More importantly, all such reports were strictly on a laboratory scale in which the electrolyzers used were simply static, beaker cell designs. As such, their usefulness is restricted to either small bench-scale preparations (0.01-1 kg) or the analytical arena, and they are not viable in a commercial or industrial setting. These beaker cells have also always used porous dividers to separate the anode and cathode compartments. The non-selective permeability of these porous dividers cause mixing of the separated solutions leading to material and efficiency losses. Attempts to use porous ceramic dividers on a commercial scale are also hampered by the mechanical fragility of such devices. Moreover, there is no suggestion in these or any other references known to appicant that alternative cell geometries and techniques which have commercial potential could be adapted for use in the field of pyridine chemistry.
With regard to selectivity during electro-oxidation, the applicant is aware of only two published reports which deal with an attempt to isolate such intermediate-stage oxidation products. Both dealt with nicotine oxidation to nicotinic acid and are conflicting. Fichter and Stenzl [Helv. Chim. Acta, 19, 1171 (1936)] reported no intermediate-stage oxidation products could be found while Yokoyama [Bull. Chem. Soc. Jpn., 7, 103 (1932)] reported hydroxynicotine and decomposition products were detected. Additionally, the applicant is aware of a report of oxidation of methylpyridines and the respective N-oxides by electrogenerated superoxide ion [H. Sagae, M. Fujihira, H Lund and T. Osa, Heterocycles, 13, 321 (1979)]. The presumed intermediate-stage aldehydes were not detected and the conclusion was that, if such materials are formed, further oxidation is rapid and no observable concentration of aldehyde is formed.